Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411
Cyanopeptolins (CPs) are one of the most frequently occurring cyanobacterial peptides, many of which are inhibitors of serine proteases. Some CP variants are also acutely toxic to aquatic organisms, especially small crustaceans. In this study, thirteen CPs, including twelve new variants, were detect...
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| Format: | Article |
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MDPI AG
2018-06-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/16/7/220 |
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| author | Hanna Mazur-Marzec Anna Fidor Marta Cegłowska Ewa Wieczerzak Magdalena Kropidłowska Marie Goua Jenny Macaskill Christine Edwards |
| author_facet | Hanna Mazur-Marzec Anna Fidor Marta Cegłowska Ewa Wieczerzak Magdalena Kropidłowska Marie Goua Jenny Macaskill Christine Edwards |
| author_sort | Hanna Mazur-Marzec |
| collection | DOAJ |
| description | Cyanopeptolins (CPs) are one of the most frequently occurring cyanobacterial peptides, many of which are inhibitors of serine proteases. Some CP variants are also acutely toxic to aquatic organisms, especially small crustaceans. In this study, thirteen CPs, including twelve new variants, were detected in the cyanobacterium Nostoc edaphicum CCNP1411 isolated from the Gulf of Gdańsk (southern Baltic Sea). Structural elucidation was performed by tandem mass spectrometry with verification by NMR for CP962 and CP985. Trypsin and chymotrypsin inhibition assays confirmed the significance of the residue adjacent to 3-amino-6-hydroxy-2-piperidone (Ahp) for the activity of the peptides. Arginine-containing CPs (CPs-Arg2) inhibited trypsin at low IC50 values (0.24–0.26 µM) and showed mild activity against chymotrypsin (IC50 3.1–3.8 µM), while tyrosine-containing CPs (CPs-Tyr2) were selectively and potently active against chymotrypsin (IC50 0.26 µM). No degradation of the peptides was observed during the enzyme assays. Neither of the CPs were active against thrombin, elastase or protein phosphatase 1. Two CPs (CP962 and CP985) had no cytotoxic effects on MCF-7 breast cancer cells. Strong and selective activity of the new cyanopeptolin variants makes them potential candidates for the development of drugs against metabolic disorders and other diseases. |
| first_indexed | 2024-04-11T13:18:48Z |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:18:48Z |
| publishDate | 2018-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-15e70a6c7481452896d1716ee0c20b0f2022-12-22T04:22:18ZengMDPI AGMarine Drugs1660-33972018-06-0116722010.3390/md16070220md16070220Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411Hanna Mazur-Marzec0Anna Fidor1Marta Cegłowska2Ewa Wieczerzak3Magdalena Kropidłowska4Marie Goua5Jenny Macaskill6Christine Edwards7Division of Marine Biotechnology, Faculty of Oceanography and Geography, University of Gdańsk, Marszałka J. Piłsudskiego 46, PL-81378 Gdynia, PolandDivision of Marine Biotechnology, Faculty of Oceanography and Geography, University of Gdańsk, Marszałka J. Piłsudskiego 46, PL-81378 Gdynia, PolandInstitute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55, PL-81712 Sopot, PolandDepartment of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, PL-80308 Gdańsk, PolandDepartment of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, PL-80308 Gdańsk, PolandSchool of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen AB10 7GJ, UKSchool of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen AB10 7GJ, UKSchool of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen AB10 7GJ, UKCyanopeptolins (CPs) are one of the most frequently occurring cyanobacterial peptides, many of which are inhibitors of serine proteases. Some CP variants are also acutely toxic to aquatic organisms, especially small crustaceans. In this study, thirteen CPs, including twelve new variants, were detected in the cyanobacterium Nostoc edaphicum CCNP1411 isolated from the Gulf of Gdańsk (southern Baltic Sea). Structural elucidation was performed by tandem mass spectrometry with verification by NMR for CP962 and CP985. Trypsin and chymotrypsin inhibition assays confirmed the significance of the residue adjacent to 3-amino-6-hydroxy-2-piperidone (Ahp) for the activity of the peptides. Arginine-containing CPs (CPs-Arg2) inhibited trypsin at low IC50 values (0.24–0.26 µM) and showed mild activity against chymotrypsin (IC50 3.1–3.8 µM), while tyrosine-containing CPs (CPs-Tyr2) were selectively and potently active against chymotrypsin (IC50 0.26 µM). No degradation of the peptides was observed during the enzyme assays. Neither of the CPs were active against thrombin, elastase or protein phosphatase 1. Two CPs (CP962 and CP985) had no cytotoxic effects on MCF-7 breast cancer cells. Strong and selective activity of the new cyanopeptolin variants makes them potential candidates for the development of drugs against metabolic disorders and other diseases.http://www.mdpi.com/1660-3397/16/7/220cyanobacteriaNostoccyanopeptolinsprotease inhibitors |
| spellingShingle | Hanna Mazur-Marzec Anna Fidor Marta Cegłowska Ewa Wieczerzak Magdalena Kropidłowska Marie Goua Jenny Macaskill Christine Edwards Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411 Marine Drugs cyanobacteria Nostoc cyanopeptolins protease inhibitors |
| title | Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411 |
| title_full | Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411 |
| title_fullStr | Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411 |
| title_full_unstemmed | Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411 |
| title_short | Cyanopeptolins with Trypsin and Chymotrypsin Inhibitory Activity from the Cyanobacterium Nostoc edaphicum CCNP1411 |
| title_sort | cyanopeptolins with trypsin and chymotrypsin inhibitory activity from the cyanobacterium nostoc edaphicum ccnp1411 |
| topic | cyanobacteria Nostoc cyanopeptolins protease inhibitors |
| url | http://www.mdpi.com/1660-3397/16/7/220 |
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